The present invention relates in general to the field of treating cerebral ischemia, and more particularly, to the use of caffeine and alcohol following a stroke to reduce cerebral infarct damage and improve the chances for complete or substantial recovery.
Without limiting the scope of the invention, its background is described in connection with the treatment of acute strokes, as an example.
Stroke is a severe, often-catastrophic disease affecting approximately 500,000 people per year in the U.S. Present methods of treatment except thrombolysis rely on supportive measures and non-specific agents. Twenty-five to sixty percent of stroke victims experience mild to severe disability, greatly increasing the long-term health related costs with aiding these patients. Therefore, there exists a need for improved methods of treating the morbidity experienced by these patients.
While intravenous thrombolytic treatments have shown promise, they generally require intervention within three hours of a stroke. Other unproven oral drug treatments may be initiated within a 24-hour post-stroke window and may positively affect neurological outcome with continued dosage for three months after a stroke.
One such method of protecting brain tissue from cerebral infarction subsequent to ischemia is disclosed in U.S. Pat. No. 5,827,832, issued to Sandage, Jr., et al. Sandage, Jr., et al. disclose an invention directed to a method of reducing the extent of infarction, and in particular, cerebral infarction subsequent to cerebral ischemia. Citicoline is administered shortly after an ischemic episode and continuing daily treatment for up to about 30 days, and in one preferred embodiment for at least about 6 weeks. The method taught is used for the treatment of stroke and severe head trauma patients and maximizes the chances for a full or substantially full recovery of the patient. The treatment regimen disclosed, however, uses citicoline, which is an exogenous form of cytidine-5xe2x80x2-diphosphocholine a key intermediate in the biosynthesis of membrane phosphatidyl choline, which is of primary importance for the dynamic regulation of cellular integrity. Furthermore the treatment protocol requires continued treatment for several weeks, with increased cost and likelihood of missing important doses.
Another method for treating central nervous system ischemia is disclosed in U.S. Pat. No. 5,571,840 issued to Mayor, et al., in which a patient who has suffered an acute insult is treated by administering an effective amount of a thyroid hormone. The thyroid hormones for use with the invention, as disclosed, include levothyroxine, liothyronine, L-3,3xe2x80x2,5xe2x80x2-triiodothyronine or L-3,5-diiodothyronine, or their sodium salts. The treatment as taught is applicable to the treatment of cerebral ischemia following cardiac arrest. The thyroid hormones, however, have known short and long term side-effects and must be used with great care under a physicians close supervision.
The present inventors have recognized the need for an effective and safe treatment for human stroke and other head related trauma. Except for the tissue plasminogen activator that is used in the clinic to recanalyze occluded vessels, there is no other effective treatment for management of stroke and related diseases. The present inventors have developed and are skilled in evaluating the efficacy of various experimental pharmacological therapies using a rat model for human stroke.
The present inventors have discovered that a composition that includes caffeine plus an alcohol, and in particular ethanol, dramatically reduces brain damage following a stroke. Like results were not observed with either caffeine or ethanol alone.
More particularly, the composition and method for protecting brain tissue from cerebral ischemia of the present invention includes administering to a subject in need thereof a dose of an effective amount of caffeine and at least a effective amount of an alcohol (i.e., an alkanol) or mixtures thereof. The mixture of alcohols may include, e.g., ethanol.
Furthermore, a composition for use in the treatment of a subject identified as having an ischemic cerebral stroke includes an effective amount of caffeine, an effective amount of an alcohol and a pharmaceutically acceptable carrier for use in treating the subject.
The composition for use with the present invention may be provided to the subject or patient in an oral, intravenous or other form that provides an effective amount of the caffeine and alcohol. The caffeine and alcohol may even be co-administered from a common source or to a common site, or be provided separately through distinct delivery sites and modes.